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WO2006098154A1 - Tonique favorisant la pousse des cheveux - Google Patents

Tonique favorisant la pousse des cheveux Download PDF

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Publication number
WO2006098154A1
WO2006098154A1 PCT/JP2006/303898 JP2006303898W WO2006098154A1 WO 2006098154 A1 WO2006098154 A1 WO 2006098154A1 JP 2006303898 W JP2006303898 W JP 2006303898W WO 2006098154 A1 WO2006098154 A1 WO 2006098154A1
Authority
WO
WIPO (PCT)
Prior art keywords
hair
rxm
growth
group
ifn
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2006/303898
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English (en)
Japanese (ja)
Inventor
Masahiro Takigawa
Taisuke Ito
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hamamatsu University School of Medicine NUC
Original Assignee
Hamamatsu University School of Medicine NUC
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from JP2005070431A external-priority patent/JP2006151938A/ja
Application filed by Hamamatsu University School of Medicine NUC filed Critical Hamamatsu University School of Medicine NUC
Publication of WO2006098154A1 publication Critical patent/WO2006098154A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/60—Sugars; Derivatives thereof
    • A61K8/602—Glycosides, e.g. rutin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • A61Q5/06—Preparations for styling the hair, e.g. by temporary shaping or colouring
    • A61Q5/065—Preparations for temporary colouring the hair, e.g. direct dyes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q7/00—Preparations for affecting hair growth

Definitions

  • the present invention relates to a hair restorer and a gray hair inhibitor containing roxithromycin.
  • Roxithromycin is a 14-membered macrolide antibiotic, and is used in many infectious diseases including skin infections. ,unknown.
  • An object of the present invention is to provide a safe and effective hair growth agent and a gray hair prevention agent.
  • RXM a component that has already been sufficiently used as a pharmaceutical and has been confirmed to be safe, has an effect of preventing apoptosis of hair tissue cells in the in vitro mouth, and has been used for both human and mouse cultured hair.
  • the present invention was completed by finding that it has the effect of significantly promoting growth and the effect of preventing human gray hair.
  • the present invention relates to a hair restorer and a gray hair inhibitor containing roxithromycin as an active ingredient.
  • the present invention can provide a hair-restoring agent and a white hair-preventing agent that are excellent in safety.
  • FIG. 1 shows the effects of RXM, EM and CLM on the growth of cultured mouse eyelashes.
  • the vertical axis represents eyelash growth (mm), and the horizontal axis represents time (days).
  • Each processing group (White square), EM5 / zM (diamond), EMIO / zM (white circle), CLM5 / zM (white triangle), CLM 10 ⁇ 1 (white square + cross), 10015 ⁇ 1 (diamond + cross), 100110 ⁇ 1 (white circle + cross).
  • FIG. 2 shows the effect of RXM on the growth of cultured mouse eyelashes in the presence of IFN-g.
  • the vertical axis represents eyelash growth (mm), and the horizontal axis represents time (days).
  • Each treatment group was indicated by control (white square), IFN—y (diamond), RXM5 M (white circle), RXM10 ⁇ (white triangle), RXMlO / zM + IFN—y (white square + cross).
  • FIG. 3 shows the effect of RXM on the hair cycle.
  • the treatment groups are, from left to right, a control group, a 50IU / mlIFN-y treatment group, a 10M RXM treatment group, and a 50IU / mlIFN-y + 10M RXM treatment group.
  • the hair cycle is growth phase VI in the Control and 10 ⁇ M RXM groups, in the regression phase in the IFN-y 50 IU / ml treatment group, and in the growth phase to early regression phase in the IFN-y + RXM treatment group. there were.
  • FIG. 4 shows the results of in situ TUNEL.
  • the treatment groups are, from the left, the control group, the 50IU / mlIFN-y treatment group, and the 50IU / mlIFN—y + 10 ⁇ 10 RXM treatment group.
  • the straight line (indicated by the arrow in the leftmost figure) that crosses the figure shows the Auber's line.
  • the cells that appear white are apoptotic cells, the number of which is 4 ⁇ 1.3 cell Z hair in the control group, and 105 ⁇ 23 cell eyelash in the 50IU / mlIFN- ⁇ treatment group, In the 50IU / mlIF N— ⁇ + 10 / zM RXM treatment group, the density was 13 ⁇ 4.3 cells Z hair.
  • FIG. 5 shows the effect of RXM on human hair growth.
  • the vertical axis represents eyelash growth (mm), and the horizontal axis represents time (days).
  • Control group (white square), RXM5 ⁇ (diamond), RXMlO / zM (white circle), ⁇ 5 / ⁇ (white triangle), ⁇ / ⁇ (white square + cross), CLM5 ⁇ (diamond + cross) ), CLM 10 ⁇ (white circle + cross).
  • FIG. 6 shows the clinical effect of RXM topical agent.
  • Roxithromycin (RXM: Erythromycin 9- ⁇ 0 — [(2-Methoxyethoxy) methyl] oxime ⁇ ) is a 14-membered macrolide antibiotic, and many infectious diseases including skin infections It is widely used for its safety and effectiveness. In addition, RX ⁇ has various immunomodulating effects in addition to its antibiotic effect. Oshima (Ohshima A, Tokura Y, Wakita H, Furukawa F, Takigawa M. Roxithromycin do wn—moduls antigen— presenting and interleukin— 1 beta-producing abilities of muri ne Langerhans cells. J Dermatol Sci 1998; 17: 214—222 .).
  • interferon ⁇ IFN-y
  • IFN-y interferon ⁇
  • RXM was also found to inhibit IFN-y-induced regressive hair and apoptotic changes.
  • Other 14-membered macrolide antibiotics clarithromycin (CLM) and erythromycin (EM) did not see such an effect, so this effect is unique to RXM.
  • roxithromycin of the present invention can be purchased.
  • an inducer of roxithromycin and a physiologically acceptable salt can be used as long as they have the effects of the present invention.
  • an anti-inflammatory agent in addition to the above, the hair-restoring agent and the gray hair-preventing agent of the present invention, if necessary, an anti-inflammatory agent
  • peripheral vasodilators tocopherol acetate, benzyl nicotinate, rapeseed extract, pepper extract, capsicum extract, etc.
  • Propionate nodule cortisone, etc. Propionate nodule cortisone, etc.
  • antihistamines diphenhydramine hydrochloride, isothibenzyl hydrochloride, etc.
  • the hair-restoring agent and the gray hair-preventing agent of the present invention can be applied to lotions, emulsions, creams, gels, aerosols, etc. according to commonly used methods, for example, methods prescribed in the 12th revised Japanese Pharmacopoeia. It can be prepared into a dosage form.
  • the dosage of the hair restorer and gray hair inhibitor of the present invention can be determined by applying an appropriate amount to the scalp once to several times a day.
  • the method for administering the hair restorer and the white hair inhibitor of the present invention is not limited, it is more preferable to use an external hair restorer that is preferably used as an oral hair restorer, an external hair restorer, or the like.
  • the content of roxithromycin hair tonic and hair graying in preventing agent of the present invention is usually 0.000 to 50 weight 0/0, preferably from 0.001 to 10 weight 0/0, more preferably 0 .
  • Ru 01-1 weight 0/0 der.
  • Examples of the form of the oral hair restorer and gray hair preventive agent of the present invention include tablets, capsules, powders, pills, powders, fine granules, granules, syrups, lozenges and the like.
  • a combination with one or more of which force is also selected may be administered as is, but together with pharmacologically acceptable excipients, tablets, capsules, powders, pills, powders, fine granules, granules, syrups May be administered in the form of an agent, a lozenge or the like.
  • Excipients include sugars such as sorbitol, ratatoose, glucose, lactose, minerals such as dextrin, starch, calcium carbonate, calcium sulfate, crystalline cellulose, distilled water, sesame oil, corn oil, olive oil, cottonseed oil, etc. Any of those generally used can be used.
  • binders, lubricants, dispersants, suspending agents, emulsifiers, dilute Additives such as a buffer, a buffer, an antioxidant, and a bacterial inhibitor can also be used.
  • Liquid or solid dosage forms include liquid dosage forms such as hair liquids, hair tonics and hair lotions, and solid dosage forms such as ointments and hair creams.
  • Phosphate buffered saline (PBS) added group control group
  • IFN— ⁇ 50 IU / ml, RX M5 ⁇ group, IFN—y 50 IU / ml + RXM10 mM group, CLM5 ⁇ M group, CLMlOmM group, EM5 ⁇ Groups and EMI OmM groups were set up.
  • each of each culture solution was added to each well, and 3 pieces of BalbZc mouse eyelashes or 3 human hairs were placed therein to start the culture.
  • the culture medium was changed every two days, and the length of the hair was measured using a stereomicroscope.
  • tissue sections stained with hematoxylin eosin were examined for morphological changes under a microscope.
  • the hair cycle score of each sample was calculated.
  • Cultured hair is known to have a shorter growth period compared to the actual hair cycle, and human cultured hair is known to enter the regression phase about 7-9 days after the start of culture.
  • the regression phase hair growth slows and apoptosis is observed in the hair matrix and proximal outer root sheath.
  • hair growth is maintained, and the number of hair matrix cells that fall into apoptosis is small. Therefore, in-situ TUNEL was performed using TUNEL kit (Apoptag, Oncor Apligene, Heidelberg, Germany) to observe apoptotic cells.
  • RXM promotes the growth of cultured mouse eyelashes, but EM and CLM do not affect the growth of cultured mouse eyelashes (Fig. 1).
  • the RXM 5mM administration group it was 3.8 mm ⁇ 0.23
  • the RXMlOmM administration group it was 4.3 mm ⁇ 0.19, which was significant in both treatment groups compared to the control group (p ⁇ 0. 01) Promotion of eyelash growth was observed.
  • the eyelash growth was 1.53 mm ⁇ 0.37, in the CLMlOmM group, 1.64 mm ⁇ 0.50, and in the EM 5 mM group, 1.68 mm O 0.42 and 1.76 mm ⁇ 0.30 in the EMIOmM group, and no significant difference was observed in the CLM and EM groups compared to the control group o
  • RXM promotes Vibrissa growth even in the presence of IFN-g ( Figure 2).
  • the concentration of IFN-y is as low as 50 IU, and such a low concentration of IFN-y has been reported to enhance MHC class I expression in hair matrix cells observed in the regression phase. (Ito et al., Collapse and restoration or MHC class- 1- dependent immune privilege: e xploiting the human hair follicle as a model. Am J Pathol 2004 164: 623-634) 0 Therefore, 50 IU / ml Concentrations of IFN-g were not employed because they were non-physiological. When cultured with RXM 10mM in the presence of IFN—y 50IU / ml, hair growth was 1.20mm ⁇ 0.06, indicating that significant (p ⁇ 0.05) hair growth was promoted. Admitted.
  • RXM inhibited the induction of regression by IFN-y and maintained the growth phase ( Figure 3).
  • the IFN-y 50 IU / ml administration group showed no significant difference compared to the control group.
  • the growth period was maintained histologically in the IFN-y 501 U / ml + RXM 10 mM administration group.
  • the reproducibility of the experimental results obtained in mice in human cultured cells was evaluated.
  • the growth amount in the RXM 5mM administration group is 3.4 mm ⁇ 0.20, and in the RXMlOmM administration group, it is 3.32 mm ⁇ 0.19. In all cases, significant (p ⁇ 0.01) hair growth was promoted compared to the control group.
  • the hair growth was 2.17 mm ⁇ 0.13
  • the CL MlOmM administration group 1.93 mm ⁇ 0.18
  • the EM 5 mM administration group 2.85 mm
  • the CLM and EM administration groups showed no significant difference compared to the control group.
  • Hair growth action is erythromycin, a 14-membered ring antibiotic with a structure similar to RXM.
  • the hair growth effect was determined according to the following method.
  • RXM solution applied for each patient Present two photos before and after application so that there is no force before and after application, select one as a photo that shows hair-growth effect, select the other as a comparison target, and determine the degree of hair-growth effect. Evaluation was made on a four-point scale: 1 point (no improvement), 2 points (mild improvement), 3 points (improvement), and 4 points (very much improved). A positive evaluation was made if the photo selected for the hair-growth effect was taken after application of RXM solution, and a negative evaluation was made before application of RXM solution. For each patient, 10 dermatologists (dermatologists certified by the Japanese Dermatological Association) judge, add the scores of each doctor, calculate the average score and standard deviation, and use it as the evaluation score. . The results are shown below.
  • RXM solution application was confirmed to be safe locally and systemically.
  • RXM solution 65 parts by weight of ethyl alcohol, 5 parts by weight of propylene glycol, 5 parts by weight of RXMO, and 29.5 parts by weight of purified water
  • RXM solution 65 parts by weight of ethyl alcohol, 5 parts by weight of propylene glycol, 5 parts by weight of RXMO, and 29.5 parts by weight of purified water
  • the growth of the eyelashes on the 6th day is 2.8 ⁇ 0.75 mm in the additive-free group, and it is ⁇ ⁇ 4.3 ⁇ 0.76 mm ( ⁇ ⁇ 0.05) in the RXM 5 mM treatment group, RXM 10 mM In the treated group, it was 3.9 ⁇ 1. Omm (p ⁇ 0. 05), and the RXM treated group showed significantly better growth than the non-added group.
  • RXM has the effect of significantly promoting hair growth in both mouse and human cultured hair and maintaining the growth period longer.
  • white hair decreased and increased black hair was also observed, so it was effective as a gray hair inhibitor.
  • RXM inhibits the induction of apoptosis by IFN- ⁇ , and therefore RXM's hair growth effect is expected even in alopecia areata, which is thought to be caused by excessive production of IFN- ⁇ . Is done. RXM is a drug that can be developed as a hair growth and alopecia treatment.
  • the hair restorer of the present invention is useful for hair growth, hair growth, alopecia treatment and prevention of white hair.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Molecular Biology (AREA)
  • Birds (AREA)
  • Dermatology (AREA)
  • Cosmetics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Tonique efficace et sans danger, favorisant la pousse des cheveux ou prévenant l’apparition de cheveux gris. L’invention concerne un tonique favorisant la pousse des cheveux ou un agent prévenant l’apparition de cheveux gris, comprenant de la roxithromycine comme ingrédient actif.
PCT/JP2006/303898 2005-03-14 2006-03-01 Tonique favorisant la pousse des cheveux Ceased WO2006098154A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2005-070431 2005-03-14
JP2005070431A JP2006151938A (ja) 2004-10-26 2005-03-14 育毛剤

Publications (1)

Publication Number Publication Date
WO2006098154A1 true WO2006098154A1 (fr) 2006-09-21

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PCT/JP2006/303898 Ceased WO2006098154A1 (fr) 2005-03-14 2006-03-01 Tonique favorisant la pousse des cheveux

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010001276A (ja) * 2008-06-18 2010-01-07 Ａｄａ Ｂｉｏ株式会社 モリブデン含有育毛・発毛剤、白髪防止剤、皮膚外用剤、分化誘導剤

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0680745A2 (fr) * 1994-05-05 1995-11-08 L'oreal Utilisation de composés antifongiques et de composés antibactériens halogénés pour diminuer la chute des cheveux
JPH09151196A (ja) * 1993-07-12 1997-06-10 Kyowa Hakko Kogyo Co Ltd トリテルペン酸誘導体
JPH1029935A (ja) * 1996-07-12 1998-02-03 Noevir Co Ltd 抗アンドロゲン剤及び養毛剤並びに毛髪用化粧料
JPH10298055A (ja) * 1997-04-22 1998-11-10 Noevir Co Ltd 抗アンドロゲン剤及び養毛剤，皮脂分泌抑制剤
JP2001131025A (ja) * 1999-11-08 2001-05-15 Shiseido Co Ltd 頭皮頭髪用化粧料

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09151196A (ja) * 1993-07-12 1997-06-10 Kyowa Hakko Kogyo Co Ltd トリテルペン酸誘導体
EP0680745A2 (fr) * 1994-05-05 1995-11-08 L'oreal Utilisation de composés antifongiques et de composés antibactériens halogénés pour diminuer la chute des cheveux
JPH1029935A (ja) * 1996-07-12 1998-02-03 Noevir Co Ltd 抗アンドロゲン剤及び養毛剤並びに毛髪用化粧料
JPH10298055A (ja) * 1997-04-22 1998-11-10 Noevir Co Ltd 抗アンドロゲン剤及び養毛剤，皮脂分泌抑制剤
JP2001131025A (ja) * 1999-11-08 2001-05-15 Shiseido Co Ltd 頭皮頭髪用化粧料

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
INUI S. ET AL.: "Modulation of androgen receptor transcriptional activity by anti-acne reagents", JOURNAL OF DERMATOLOGICAL SCIENCE, vol. 36, no. 2, 2004, pages 97 - 101, XP004616054 *
INUI S. ET AL.: "Potential antiandrogenic activity of roxithromycin in skin", JOURNAL OF DERMATOLOGICAL SCIENCE, vol. 27, no. 2, 2001, pages 147 - 151, XP003000018 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2010001276A (ja) * 2008-06-18 2010-01-07 Ａｄａ Ｂｉｏ株式会社 モリブデン含有育毛・発毛剤、白髪防止剤、皮膚外用剤、分化誘導剤

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